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Polyunsaturated fatty acids, maternal and infant immune responses and allergic disease in infancy
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The incidence of allergic diseases in industrialized countries has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcome in the child.

Aim: The aim of this thesis was to add knowledge on the relationship between long chain polyunsaturated fatty acids, sensitization and allergic disease and possible immunological events regulating this.

Subjects: The thesis is based on results obtained from two cohorts. The first, including 300 cord blood samples collected from 1985-2005. The second, a double-blind placebo controlled multi-centre study comprising 145 families with allergic disease.

Methods: Phospholipid fatty acids and total IgE antibodies were analyzed in cord blood samples with gas chromatography and Uni-CAP™, respectively.

The families participating in the double-blind placebo controlled multi-centre study were recruited at antenatal units in Linköping and Jönköping and the mothers were supplemented with 2.6 g ω-3 long-chain polyunsaturated fatty acids (LCPUFA) or placebo daily from gestational week 25 until 3 months of breast feeding. Phospholipid fatty acids in maternal serum were analysed before and during the intervention to assess compliance. Prostaglandin E2, leukotrienes B4 and cytokines were analyzed with ELISA technique in supernatants from maternal LPS-stimulated whole blood cultures. Clinical outcome was allergic disease with positive skin prick test and/or specific circulating IgE to food allergens at one year of age. Cytokines, chemokines, SIgA antibodies and prostaglandin E2 were analyzed in breast milk with Luminex and ELISA techniques.

Results: The proportions of cord serum linoleic acid (LA, C18:2 ω-6) and α-linolenic acid (LNA, C18:3 ω-3) decreased significantly from 1985 to 2005. However, the LA/LNA ratio did increase, revealing a relatively larger decrease in LNA than in LA. The proportions of both arachidonic acid (AA; C20:4 ω-6) and docosahexaenoic acid (DHA, C22:6 ω-3) as well as other ω-6 and ω-3 fatty acids increased significantly during the same time period. No correlations were found between ω-6 and ω-3 fatty acids and total IgE antibodies.

Proportions of ω-3 LCPUFA increased in the ω-3 supplemented group of mothers.

Lipopolysaccharide-induced prostaglandin E2 secretion in whole blood culture decreased in a majority of ω-3 PUFA supplemented mothers (18 of 28, p < 0.002).The decreased prostaglandin E2 production was more pronounced among non-atopic than atopic mothers. Lipopolysaccharide induced cytokine and chemokine secretion was not affected. The period prevalence of food allergy was lower in the ω-3 group (1⁄52, 2%) compared to the placebo group (10⁄65, 15%, p <0.05) as well as the incidence of IgE-associated eczema (ω-3 group: 4 ⁄ 52, 8%; placebo group: 15 ⁄ 63, 24%, p < 0.05) at one of year. There were no differences in breast milk cytokine, SIgA and PGE2 levels between the two intervention groups. However, the levels of several cytokines tended to be higher in colostrum from non-atopic ω-3 supplemented mothers as compared to non-atopic placebo supplemented mothers. Higher levels of TGFß2 and SIgA in 3 months milk were associated with allergic disease at one year of age both with and without detectable IgE.

Conclusions: Cord blood LA proportions decreased and LA/LNA ratio increased over the 20 year period between 1985 and 2005 this was not related to total IgE. ω-3 fatty acid supplementation of pregnant and lactating mothers resulted in a lower period prevalence of IgE associated eczema and food allergy in the children at one year of age. This was most pronounced in children of non-allergic mothers. The underlying mechanism requires further clarification.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2010. , p. 97
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1182
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-56265ISBN: 978-91-7393-400-8 (print)OAI: oai:DiVA.org:liu-56265DiVA, id: diva2:317856
Public defence
2010-06-07, Linden, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:30 (Swedish)
Opponent
Supervisors
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2021-02-25Bibliographically approved
List of papers
1. Decreased proportions of linoleic acid (LA) in cord blood samples collected between 1985 and 2005
Open this publication in new window or tab >>Decreased proportions of linoleic acid (LA) in cord blood samples collected between 1985 and 2005
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Cord serum (CS) phospholipid fatty acid composition is influenced by the maternal diet during foetal life and maternal intake of LA and LNA has been shown to influence the LA and LNA levels in CS. A possible connection between the increased incidence of atopic diseases and the simultaneous increased intake of linoleic acid (LA, C18:2ω-6) and decreased intake of α-linolenic acid (LNA, C18:3 ω-3) in the western world has been proposed.

The aim of this study was to explore phospholipid fatty acid proportions and total IgE levels in CS collected from 1985 to 2005 from Swedish children, in a period with increasing frequency of allergic diseases in Sweden, and reveal possible changes over time. Omega (ω)-6 and ω-3 fatty acids and total IgE antibodies were analysed with gas chromatography and UniCAP® technology respectively in a total of 300 CS samples (60 samples every fifth year).

The proportions of linoleic acid (LA, C18:2 ω-6) and α-linolenic acid (LNA, C18:3 ω-3) decreased significantly from 1985 to 2005. However, the LA/LNA ratio did increase revealing a relatively larger decrease in LNA than in LA. The proportions of both arachidonic acid (AA; C20:4 ω-6) and docosahexaenoic acid (DHA, C22:6 ω-3) as well as other ω-6 and ω-3 fatty acids increased significantly during the same time period. No correlations were found between ω-6 and ω-3 fatty acids and total IgE levels in CS from newborn infants.

Keywords
Arachidonic acid, cord blood, linoleic acid, omega-6 fatty acids, omega-3 fatty acids, total IgE
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-56263 (URN)
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2021-02-25
2. The Effects of Omega-3 Fatty Acid Supplementation in Pregnancy on Maternal Eicosanoid, Cytokine, and Chemokine Secretion
Open this publication in new window or tab >>The Effects of Omega-3 Fatty Acid Supplementation in Pregnancy on Maternal Eicosanoid, Cytokine, and Chemokine Secretion
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2009 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 66, no 2, p. 212-217Article in journal (Refereed) Published
Abstract [en]

The incidence of allergic diseases has increased, and,I relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this Study was to determine the effects of omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFA) Supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E, secretion from whole blood culture supernatants (it = 59) decreased in a majority of the omega-3-supplemented mothers (18 of 28, p = 0.002). The decreased prostaglandin E-2, production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced cytokine and chemokine secretion was not affected. Out results indicate that omega-3 LCPUFA supplementation during the last trimester may dampen certain immune responses involved in allergic inflammation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20127 (URN)10.1203/PDR.0b013e3181aabd1c (DOI)
Available from: 2009-08-31 Created: 2009-08-31 Last updated: 2021-02-25
3. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy
Open this publication in new window or tab >>Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy
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2009 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 9, p. 1461-1467Article in journal (Refereed) Published
Abstract [en]

Maternal intake of omega-3 (-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. Aim: To describe the effects of maternal -3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. Methods: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. Results: The period prevalence of food allergy was lower in the -3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p andlt; 0.05) as well as the incidence of IgE-associated eczema (-3 group: 4/52, 8%; placebo group: 15/63, 24%, p andlt; 0.05). Conclusion: Maternal -3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.

Keywords
Allergy, Eczema, Lactation, Polyunsaturated fatty acids, Pregnancy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19806 (URN)10.1111/j.1651-2227.2009.01355.x (DOI)
Available from: 2009-08-11 Created: 2009-08-10 Last updated: 2021-02-25
4. Omega-3 long chain polyunsaturated fatty acid supplementation in pregnancy and lactation and immune components in breast milk
Open this publication in new window or tab >>Omega-3 long chain polyunsaturated fatty acid supplementation in pregnancy and lactation and immune components in breast milk
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Human milk transfers important immunological information from mother to child. We have previously reported lower prevalence of IgE-mediated disease at 12 months after maternal supplementation with ω-3 long chain polyunsaturated fatty acid (LCPUFA) during pregnancy and lactation. Our aim was to explore the effect of ω-3 LCPUFA on the immune composition of human milk in relation to maternal atopy and allergic disease in the offspring. Pregnant women in families with a history of allergic disease were supplemented daily with 2.7 g ω-3 LCPUFA or 2.8 g soybean oil as placebo from late pregnancy to three months of lactation. Milk samples from colostrum (n=107), at 1 mo (n=102) and at 3 mo (n=95) were analyzed for IL-1ß, IL-2, IL-4, IL-5, IL-6, CXCL-8, IL-10, IL-12p40/p70, IL-13, GM-CSF, TNF, IFN-γ, PGE2, TSLP, TGF-ß2 and SIgA with multiplex assay or ELISA. The levels of several cytokines were higher in non-atopic ω-3 supplemented mothers as compared to placebo supplemented mothers regardless of atopic status. Higher levels of TGFß2 and SIgA in 3 months milk were associated with allergic disease at one year of age both with and without detectable IgE. These results suggest that ω-3 LCPUFA supplementation during pregnancy influences cytokine levels in breast milk especially in non-atopic mothers.

Identifiers
urn:nbn:se:liu:diva-56264 (URN)
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2021-02-25

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